Postprostatectomy PSA May Predict Salvage RT Benefit

Action Points

The benefits of salvage radiotherapy after radical prostatectomy for prostate cancer varied significantly by the duration of delay to salvage therapy, PSA dynamics, and other prostatectomy-related factors.

Note that the findings suggest that prolonged monitoring of detectable post-radical prostatectomy PSA levels that delays initiation of salvage radiotherapy may not be the best strategy.

The benefits of salvage radiotherapy after radical prostatectomy varied significantly by the duration of delay to salvage therapy, PSA dynamics, and other prostatectomy-related factors, a large retrospective review showed.

Initiating salvage radiotherapy at a postprostatectomy PSA level ≤0.5 ng/mL was associated with significantly lower rates of biochemical relapse, distant metastasis, and cause-specific mortality at 5 and 10 years, as compared with receipt of salvage therapy at higher PSA levels.

Receipt of salvage therapy at postprostatectomy PSA levels ≤0.5 ng/mL led to about a 10-point absolute improvement in overall survival (OS) at 10 years, although the difference did not achieve statistical significance, reported Thomas Pisansky, MD, of the Mayo Clinic in Rochester, Minn., and colleagues online in theJournal of Clinical Oncology.

"These observations reaffirm findings of previous studies but also demonstrate, for the first time to our knowledge, the benefit of early salvage radiotherapy related to survival outcomes," the authors concluded.

"Taken together, these findings argue against prolonged monitoring of detectable post-radical prostatectomy PSA levels that delays initiation of salvage radiotherapy and serve as an important component of shared decision making between patient and physician," they added.

As the authors acknowledged, the study reinforces findings from previous investigations into the relationships among PSA level, salvage radiotherapy, and outcomes in prostate cancer, said David Beyer, MD, of Cancer Centers of Northern Arizona in Sedona.

"This study is very good to see, and it does break a little new ground," Beyer, president of the American Society for Radiation Oncology (ASTRO), told MedPage Today. "What they've done that's different from previous studies is that they've gone on to show why it's better to give the salvage therapy early."

Studies established PSA level at the time of salvage radiotherapy as prognostic for subsequent risk of biochemical relapse. However, the association between PSA at salvage therapy and distant metastasis or cause-specific mortality remained unclear. Pisansky and colleagues addressed the unresolved issue in a retrospective review of 1,067 who received postprostatectomy salvage radiotherapy from January 1987 to July 2013.

Analysis of baseline characteristics showed that a majority of the patients had pathologic stage T2 (56.2%) or T3a (27.4%) prostate cancer, and 98.3% did not have nodal involvement. About 30% of the men had Gleason grade ≤6 disease and 49.7% had Gleason 7. A similar proportion of patients (49%) had positive and negative surgical margins, and pre-salvage radiotherapy PSA level was ≤0.5 ng/mL in 45.3% of cases. Almost 85% of the men received no androgen deprivation therapy (ADT).

Total radiation dose was:

<66 Gy in 30.7%

66 to 67.99 Gy in 17.8%

68 to 71.99 Gy in 34.7%

≥72 Gy in 16.8%

During a median follow-up of 8.9 years, biochemical relapse occurred in 54% of the patients, resulting in a 5-year biochemical relapse rate of 49.9%, increasing to 64.3% at 10 years. Multivariate analysis showed that increasing tumor stage, Gleason score, and PSA at salvage therapy increased the likelihood of biochemical relapse, whereas a cumulative radiotherapy dose ≥68 Gy and receipt of ADT reduced the likelihood.

The authors reported that 208 patients developed distant metastasis, resulting in 5- and 10-year incidences of 10.9% and 19.9%, respectively. By multivariate analysis, pathologic T3b and Gleason ≥7 increased the risk of distant metastasis.

The data showed that 280 patients died during follow-up, including 110 deaths attributed to prostate cancer. OS was 92.9% at 5 years and 77.3% at 10 years. Cause-specific mortality was 3.0% and 10.4% at 5 and 10 years, respectively.

Each doubling of the PSA level at the time of salvage radiotherapy increased the risk of biochemical relapse by 30% (P<0.001), distant metastasis by 32% (P<0.001), cause-specific mortality by 40% (P<0.001), and overall mortality by 12% (P=0.02).

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